The overall objective of this project is to further our understanding of the metabolism of triglyceride rich particles and production of low density lipoproteins. Central to this will be studies on the role of heparin releasable lipase enzymes, lipoprotein lipase and hepatic triglyceride lipase. The cynomolgus monkey has been developed as a model for studying lipoprotein metabolism in primates. By infusion or specific antisera, animals will be produced which are deficient in either or both enzymes. In vivo inhibition of the enzymes will be documented. We have shown that inhibition of hepatic triglyceride lipase is associated with an alteration in very low density lipoprotein metabolism during an acute infusion of antisera. Studies will be conducted to assess lipid and apolipoprotein composition during this inhibition. Chronic inhibition of the enzyme will also be performed as will studies of human chylomicron metabolism and artificial emulsions during this inhibition. Similar studies will be performed during inhibition of lipoprotein lipase in the monkey. Finally studies will be performed during inhibition of both enzymes to assess non-lipase removal of these particles. The epidemiologic association of low density lipoprotein levels and human coronary artery disease makes understanding of the production of low density lipoproteins of major concern. Additionally, the physiologic alterations occurring in patients with Primary Type I Hyperlipoproteinemia (deficient in lipoprotein lipase) may be clarified by our results.